This work is intended ultimately to elucidate the mechanisms which control the overall rate of protein synthesis in normal and neoplastic mammalian tissues. Utilizing the Ehrlich ascites tumor cell, we are studying polypeptide chain elongation and polypeptide chain initiation, both of which have been shown to be involved in the control of the rate of protein synthesis during nutritional deprivation. 1) Elongation, Several macromolecular components catalyzing elongation, namely EEF1 and EF2, as well as the polyribosome-associated proteins and macromolecular inhibitors of elongation are being assessed in control and nutritionally deprived cells to determine which are rate-limiting and which can be modulated. 2) Initiation. We are studying the binding of Met-tRNA to the native 40S ribosomal subunit, and the IF2-like initiation factor required for its binding, to provide further evidence for the hypothesis that various forms of the native 40S subunit contain different bound initiation factors and are intermediate complexes representing stages in the formation of the complete initiation complex.